JP5201742B2 - Instrument for cardiovascular therapy - Google Patents

Description

  The present invention relates to cardiac rhythm management instruments such as pacemakers and other implantable instruments.

[Description of related applications]
This application is a priority application of US patent application Ser. No. 11 / 566,896, filed on Dec. 5, 2006, which is incorporated herein by reference, the contents of which are incorporated herein by reference. Part.

  Myocardial ischemia refers to a condition in which blood supply to a region of the myocardium (ie, the myocardium) is greatly impaired, and adequate oxygen for oxidative metabolism is not supplied to this region. Ischemia is associated with reduced metabolic byproduct removal, unlike hypoxia, where perfusion is not reduced. The heart is an aerobic (aerobic) organ that generates most of the energy from the oxidation of substances by oxygen sent by the blood. The heart can produce a slight oxygen deficiency and is therefore very sensitive to disruption of the blood supply. Myocardial ischemia occurs when there is an imbalance between oxygen supply and oxygen demand as a result of increased myocardial oxygen demand, decreased myocardial oxygen supply, or both. Due to myocardial ischemia, many patients experience chest pain or discomfort called angina. Angina pectoris serves as a useful warning of inadequate myocardial perfusion, which can lead to more severe conditions such as heart attacks or cardiac arrhythmias.

  Coronary artery disease (CAD) occurs when the coronary artery that supplies blood to the myocardium becomes hardened and stenotic due to the deposition of atherosclerotic plaque. Atherosclerotic plaques are inflammatory reaction sites in the walls of arteries and are composed of a core containing inflammatory cells surrounded by lipids and connective tissue capsules. Myocardial infarction (MI) or heart attack is when an atherosclerotic plaque in the coronary artery ruptures, thereby exposing blood to a lipid core that has a high degree of thrombogenic plaque formation (thrombosis) in the artery. To happen. Complete or near-complete occlusion to coronary blood flow can damage a fairly large area of heart tissue and cause sudden death, usually due to abnormal heart rhythms that prevent effective pumping (cardiac pump function). is there.

  The presence of coronary artery occlusion due to CAD may result in temporary imbalances in oxygen supply and demand due to increased myocardial oxygen requirements caused, for example, by physical exertion or emotional distress. Such demand ischemia may cause a condition called exertional angina or chronic stable angina. In other situations, imbalance may occur acutely due to a sudden decrease in blood flow, sometimes referred to as supply ischemia. Acute blood flow disruption may occur following coronary vasospasm, causing a condition called unstable angina. As described above, acute blood flow disruption may also occur due to coronary thrombosis causing MI. Myocardial ischemia often occurs due to both increased oxygen demand and decreased supply.

  According to the present invention, it is a cardiac instrument that can be connected to an implantable housing that houses an electrical circuit, a vasoactive stimulation electrode that is arranged proximate to a coronary artery, and a vasoactive stimulation electrode. A pulse generator that outputs a vasoactive stimulation pulse, a sensing channel that senses (detects) cardiac electrical activity, and a normal mode in which no vasoactive stimulation pulse is delivered or a vasoactive stimulation pulse causes vasodilation of the coronary artery And a controller programmed to operate in a vasodilation mode that is delivered in such a manner.

FIG. 2 illustrates the physical configuration of an exemplary pacing instrument. FIG. 2 illustrates components of an example instrument. 1 is a block diagram of electronic circuitry of an exemplary instrument. It is a figure which shows the example arrangement | positioning place of a vasoactive stimulation electrode. FIG. 3 illustrates an exemplary embodiment of a vasoactive stimulation lead. FIG. 6 is a diagram illustrating an exemplary algorithm that employs inlet and outlet conditions for switching to a vasoactive mode. FIG. 6 is a diagram illustrating an example algorithm that switches between a normal mode, a vasoconstriction mode, and a vasodilation mode.

  Myocardial ischemia is usually treated with agents that act to either increase myocardial perfusion or decrease myocardial oxygen demand. Surgical revascularization (revascularization) procedures may also be performed to increase blood supply. As used herein, to treat myocardial ischemia employing electrical stimulation that can be delivered by, for example, an implantable cardiac instrument to cause vasodilation and / or vasoconstriction of one or more coronary arteries. Another intervention is disclosed.

Coronary vasoactive electrical stimulation As used herein, “vasoactive therapy” is electrical stimulation that is exerted on a blood vessel in a manner that causes either vasoconstriction or vasodilation. It can be said that electrical stimulation pulses applied to an artery can cause arterial contraction when these pulses are applied at one frequency and can cause arterial dilation when the pulse is applied at another frequency. Found experimentally. For example, as found in experiments involving aortic stimulation, dilation occurs with low frequency (eg, about 1 Hz) stimulation and contraction with high frequency (eg, about 16 Hz) stimulation. The stimulation parameters that cause vasodilation or vasoconstriction can vary depending on the particular artery and the particular patient. Disclosed herein is an implantable pulse generator instrument and lead system that may be configured to stimulate one or more coronary arteries to cause vasodilation and / or vasoconstriction. The instrument can deliver vasodilatory stimuli to relieve symptoms of angina and / or prevent myocardial infarction, and to one or more sensed variables that indicate myocardial ischemia. In response and / or in response to commands received by telemetry or other means, vasodilator stimulation can be delivered. The instrument intermittently applies vasoconstriction stimuli according to a defined schedule and / or in response to one or more sensed variables to intentionally stress the heart and prepare it. Can be sent out automatically. This vasoconstriction causes intermittent ischemia to produce a therapeutic effect similar to exercise. Due to such intermittent events of myocardial ischemia, the heart can better tolerate subsequent events of naturally occurring ischemia and / or cause angiogenesis to improve the heart's blood supply.

  In order for the implantable pulse generator to provide vasoactive therapy to the heart, the stimulation electrode may be positioned directly on the epicardium on the coronary artery. In another approach, the stimulation lead is placed in the coronary sinus or cardiac vein adjacent to the target artery, eg, the left circumflex coronary artery or the left anterior descending coronary artery. A stimulation electrode may also be placed in the right ventricle to target the right coronary artery using a similar method. Next, the stimulation parameters are adjusted while monitoring myocardial blood flow (eg, by coronary angiography or electrocardiography) to identify the optimal parameters for causing vasoconstriction and / or vasodilation in a particular patient. Is good. Such stimulation parameters include pulse frequency, stimulation polarity (anode or cathode), pulse amplitude, pulse width, stimulation vector, and stimulation burst duration. Stimulation may be timed by the cardiac cycle to occur selectively during systole or diastole. Information about systole and diastole can be obtained from local electrogram signals, impedance measurements, heart sounds, pressure signals or ECG.

  As described above, an implantable cardiac instrument may include one or more electrodes that are placed at a site proximate to the coronary artery. In this case, the instrument may be programmed to operate in a vasodilation mode that delivers stimulation pulses in a manner that causes dilation of the coronary arteries. In one embodiment, the stimulation pulse may be delivered while the heart is in a refractory (non-responsive) period determined by sensed cardiac electrical activity. In another embodiment, in addition to or instead of delivering a stimulus while the heart is in the refractory period, the stimulation pulse is a systolic phase determined from a local electrogram signal, impedance measurement, heart sound or pressure signal. Or it may be timed by the cardiac cycle to occur selectively during diastole. Vasodilation increases myocardial blood flow and reduces ischemia that may be present. The instrument may be programmed to operate intermittently in the vasodilation mode when the instrument returns to the normal mode when the vasodilation mode ends. In the normal mode and / or vasodilation mode, the instrument may perform additional therapies such as bradycardia or cardiac resynchronization pacing and / or anti-tachyarrhythmia therapy such as anti-tachycardia pacing and cardioversion / fibrillation Dynamic removal can be applied concomitantly. This instrument can be used to enter one or more of the following inlet conditions, for example: 1) activation of a patient operated switch that can be operated by the patient when an angina occurs; The normal mode can be switched to the vasodilation mode according to the reception of the telemetry command and / or the presence of the myocardial ischemia sensed by the instrument according to the sensed variable correlated with the presence of the myocardial ischemia. Examples of sensed variables that reflect myocardial ischemia include the sensed cardiac electrical activity, non-electrical means (eg, heart sounds or pressure signals) and / or patients with demand ischemia at the effort level Features derived from related variables such as heart rate, minute ventilation and activity level. Vasodilation mode may also be terminated upon detection of one or more specified events or conditions, referred to as exit conditions. Such exit conditions include, for example, non-detection of the presence of myocardial ischemia, elapsed time, activation of a patient-operated switch and / or receipt of a telemetry command that terminates the mode.

  As mentioned above, another use of vasoactive therapy in the treatment of myocardial ischemia intentionally stresses the heart by intermittently producing low levels of myocardial ischemia, thereby promoting angiogenesis. In some cases, the heart is pre-prepared to better withstand the effects of the next ischemic event. Thus, the instrument is configured to intermittently switch from normal mode or vasodilation mode to a vasoconstriction mode that delivers stimulation to one or more coronary artery sites in a manner that causes vasoconstriction. Is good. As in the case of vasodilator stimulation described above, vasoconstriction stimuli may be delivered during the cardiac refractory period and / or timed by the cardiac cycle to selectively cause vasoconstriction stimulation during systole or diastole It is good to do so. Intermittent switching to vasoconstriction mode may be controlled according to one or more inlet conditions or one or more outlet conditions, where such inlet and outlet conditions include elapsed time, Examples include heart rate, activity level measured by an accelerometer, and minute ventilation. Vasoconstriction mode is designed to produce low-level myocardial ischemia, so only if the patient is at rest and is not experiencing an ischemic event because of increased metabolic demand or decreased blood supply It is desirable to employ a vasoconstriction mode. For example, the entry condition to enter the vasoconstriction mode may be that the measured heart rate and / or effort level is below some specified threshold, and the exit condition to exit the vasoconstriction mode is measured The heart rate and / or effort level may be higher than some specified threshold. The additional entry and exit conditions are elapsed time based on a schedule defined to enter the vasoconstriction mode only at certain points in the day and / or limit the duration of such vasoconstriction mode. Is good.

Exemplary Implantable Instrument FIG. 1 illustrates an implantable pulse generator 100 that applies vasoactive therapy and possibly other types of therapy to the heart. Implantable cardiac devices, such as pacemakers, are typically intravenously inserted into the heart so that a lead is placed in the heart chamber and connected to electrodes used for sensing and / or stimulation. Placed subcutaneously or submuscularly in the patient's chest. The electrode may be positioned on the epicardium by various means. FIG. 1 shows an exemplary instrument with two leads 200, 300, each lead being a multipolar (ie, multi-electrode) lead with electrodes 201, 202 and electrodes 301-304, respectively. is there. Electrodes 201, 202 are placed in the right ventricle to sense cardiac electrical activity and possibly provide pacing therapy. Electrodes 301-304 are placed in the coronary sinus to stimulate the left circumflex coronary artery. The instrument includes additional leads and / or electrodes and / or pacing vectors to stimulate additional arterial sites and / or provide pacing therapy to one or more myocardial sites There is. The instrument senses intrinsic cardiac electrical activity through one or more sensing channels and delivers vasoactive stimulation (or pacing pulses) through one or more stimulation channels, each such A channel has one or more of the electrodes, a pacing configuration (ie monopolar or bipolar) and a pacing vector. A programmable electronic controller is responsive to elapsed time and / or sensed cardiac electrical activity (ie, intrinsic heartbeat not as a result of the pacing pulse) and vasoactive stimulation pulses and / or pacing. Controls the delivery of pulses. As mentioned above, it may be desirable to deliver vasoactive stimulation pulses while the heart is in a refractory period. The refractory period of the heart can be defined as a specified time following a ventricular sense or a ventricular pace. Depending on the cardiovascular of interest, the stimulation may be based on a flow pattern in the blood vessel other than the refractory period. Such a flow pattern can be estimated from cardiac electrical activity or measured by an impedance sensor for measuring blood flow. Vasoactive stimuli can also be timed out to specific portions of the mechanical heart cycle determined from impedance measurements representing cardiac blood flow. Coronary blood flow is most common, for example, during diastole, and during this period it may be desirable to dilate or contract the coronary blood vessels.

  FIG. 2 illustrates the components of the implantable instrument 100 in detail and illustrates an exemplary monitor / programming system. The implantable device 100 has a hermetically sealed housing 130 that is placed subcutaneously or submuscularly in a patient's chest. The housing 130 may be made of a conductive metal, such as titanium, which can serve as an electrode for delivering electrical stimulation or sensing in a monopolar configuration. A header 140, which may be made of an insulating material, is attached to the housing 130 for receiving the leads 200, 300, which are in this case electrically connected to the pulse generation circuit and / or the sensing circuit. It is good. Housed within the housing 130 is an electronic circuit 132 that provides functionality to the devices described herein, which is programmable to control the operation of the power supply, sensing circuit, pulse generation circuit, and instrument. There may be a telemetry transceiver that can communicate with the electronic controller and external programmer or remote monitor device 190. An external programmer communicates wirelessly with the instrument 100 so that the clinician can receive data and change the controller's programming. The remote monitoring device also communicates with the instrument 100 via telemetry methods and can be further interfaced to a network 195 (eg, an internet connection) that communicates with the patient management server 196, which allows the clinical practitioner to You can be in a remote location and receive information or issue commands from a remote monitoring device. When a specific condition is detected (eg, when a measurement parameter exceeds or falls below a specified limit), the instrument sends a warning message to the remote monitoring device and to the patient management server for clinical engagement. It should be programmed to alert the person.

  A block diagram of circuit 132 is shown in FIG. A battery 22 supplies power to the circuit. The controller 10 controls the overall operation of the instrument according to programmed instructions and / or circuit configurations. The controller may be embodied as a microprocessor-based controller, such a controller having a microprocessor and memory for storing data and programs, and a dedicated hardware component such as an ASIC (eg, a finite state machine). Or may be embodied as a combination thereof. The controller further includes a timing circuit, such as an external clock, that embodies a timer used to measure elapsed time and schedule events. As used herein, the term “controller programming” refers to a specific configuration of hardware components that perform code or specific functions that are executed by a microprocessor. The sensing circuit 30 and the pulse generation circuit 20 are interfaced to the controller, and the controller 30 interprets the sensing signal and controls the delivery of the stimulation pulse by the circuits 30 and 20. The sensing circuit 30 receives atrial and / or ventricular electrogram signals from the sensing electrodes, the sensing circuit comprising a sensing amplifier, an analog-to-digital converter that digitizes the sensing signal input from the sensing amplifier, and the gain of the sensing amplifier and It has a writable register to adjust the threshold. The pulse generation circuit 20 delivers stimulation pulses to electrodes arranged for vasoactive stimulation or pacing, the pulse generation circuit comprising capacitive discharge pulse generators, registers controlling the pulse generators and stimulation parameters such as pulses Has registers to adjust energy (eg, pulse amplitude and width) and frequency. To adjust the stimulation parameters, the instrument is connected via a telemetry interface according to electrophysiological and / or angiographic tests to determine parameters suitable for producing vasoconstriction and / or vasodilation of the target artery. Good to program. The pulse generation circuit may further include a shock pulse generator for delivering a defibrillation / cardiac defibrillation shock via the shock electrode when detecting an anti-tachyarrhythmia. A telemetry transceiver 80 is interfaced to the controller such that the controller can communicate with an external programmer and / or a remote monitor unit. A magnetically actuated or contact actuated switch 24 is also shown interfaced to the controller so that the patient can signal certain conditions or events to the implantable instrument. Also, pacing or vasoactive stimulation, eg activity level (eg accelerometer), heart rate, ventilation per minute, heart blood flow and / or chest impedance to indicate cardiac cycle timing, cardiac output, blood pressure Can be used to control blood oxygen, blood pH, blood enzymes (eg, CK-MB, troponin, etc.) and myocardial contractility (eg, indicated by maximum dP / dt measured by arterial pressure sensor) One or more sensors 25 that sense physiological variables are interfaced.

The stimulation channel is composed of a pulse generator connected to the electrode, and the sensing channel is composed of a sense amplifier connected to the electrode. Electrodes 40 ₁ to 40 _N are shown, where N is an integer. The electrodes may be located on the same or different leads, and such electrodes are electrically connected to the MOS switch matrix 70. The switch matrix 70 is controlled by the controller, and this switch matrix is used to switch the selected electrode to the sense amplifier input or pulse generator output to configure the sensing or stimulation channel, respectively. The instrument may comprise any number of pulse generators, amplifiers and electrodes that can be arbitrarily combined to form sensing or stimulation channels and vectors. The stimulation channel may be configured as a vasoactive stimulation channel or pacing channel. The instrument shown in FIG. 3 is equipped with multiple sensing and / or stimulation channels, which can be either the atrial or ventricular sensing / pacing channel or the vasoactive stimulation channel, depending on the location of the electrodes. It is good to be configured. The stimulation channel can also act as either a vasoactive stimulation channel or a pacing channel, depending on the timing and type of stimulation pulses delivered. Stimulation and sensing channel configuration can be performed automatically by an instrument by an external programmer communicating via a telemetry interface and upon switching to or from various operating modes.

  The switch matrix 70 also allows a selected one of the available implanted electrodes to be incorporated into the sensing and / or stimulation channel in either a monopolar or bipolar configuration. Bipolar sensing or stimulation configuration means the sensing of a potential or the output of a stimulation pulse between two closely spaced electrodes, where the two electrodes are usually located on the same lead (e.g. , Two selected electrodes, a ring of bipolar leads and a tip electrode or multipolar lead). A monopolar sensing or stimulation configuration is where the sensed potential or stimulation pulse output by the electrode is referenced to the conductive instrument housing or another remotely located electrode.

Detection of myocardial ischemia When the blood supply to a region of the myocardium is compromised, the supply of oxygen and other nutrients is insufficient for the cardiomyocyte metabolic process to maintain these normal polarization states There is a case. Thus, the ischemic region of the heart becomes abnormally depolarized during at least a portion of the cardiac cycle, causing current to flow between the ischemic region of the heart and the normally polarized region, which is damaged. Called current. The injury current may be caused by an infarct that is permanently depolarized or by an ischemic region that remains abnormally depolarized during all or part of the cardiac cycle. Ischemia and infarction can affect the magnitude of depolarization and the rate at which depolarization moves through the myocardium. All of these effects result in abnormal changes in the potential caused by cardiac excitation reflected by either surface electrocardiogram or intracardiac electrogram. Accordingly, the instrument may be configured to detect the presence of myocardial ischemia from one or more sensed variables associated with cardiac electrical activity.

  The instrument may be configured to detect cardiac ischemia from morphological analysis of the electrocardiogram collected during the intrinsic or paced heartbeat, the latter heartbeat being an evoked response and Sometimes called. As described above, an abnormal change in the potential measured by the intracardiac electrogram occurs as a result of the damaging current. If abnormal ventricular depolarization continues throughout the cardiac cycle, a zero potential is measured only when the rest of the ventricular myocardium is depolarized, which is between the end of the QRS complex of the electrogram and the T-wave. It corresponds to time and is called ST (Estee) wave. After ventricular depolarization, clearly indicated by the T wave of the electrogram, the measured potential is affected by the injury current and is shifted positively or negatively with respect to the ST wave depending on the location of the ischemic or infarcted area. Will come to be. Traditionally, however, it is the ST wave that is considered shifted when an abnormal damage current is detected by an electrogram or electrocardiogram. Damage currents caused by ischemic regions that do not last throughout the cardiac cycle may only shift part of the ST wave, resulting in an abnormal gradient of the ST wave. Damage currents can also occur when ischemia causes prolonged depolarization in the ventricular region, resulting in an abnormal T wave when the direction of the repolarization wave changes. In order for the instrument to sense changes in the electrogram representing ischemia, the recorded electrogram is analyzed and compared to a reference electrogram, which is either the entire recorded electrogram or a specific electrogram representing the electrogram It should be one of the reference values. Since certain patients may always show damaging currents in the electrogram (eg, due to CAD or as a result of electrode implantation), the controller compares the recorded electrogram with the reference electrogram. It may be programmed to sense ischemia by looking for an increase in the damaging current, and the reference electrogram may or may not indicate the damaging current. One approach to look for an increase in damage current in the recorded electrogram is to compare the ST wave amplitude and / or slope to the reference electrogram amplitude and slope. For example, various digital signal processing techniques can be used for analysis using the first and second derivatives to identify the start and end of the ST wave. In another method for searching for the damage current, for example, the recording electrogram and the reference electrogram are cross-correlated to determine their similarity. In this case, the electrogram may be implicitly recorded by passing the electrogram signal through a matched filter that cross-correlates the signal to a reference electrogram. Further, the ST wave may be integrated, and as a result, the integrated value is compared with the reference value to determine whether there is an increase in damage current.

  As noted above, other sensed variables may also indicate the presence of myocardial ischemia, particularly in patients with exertional angina. Thus, the instrument is based on sensed variables such as heart rate, activity level, local heart motion, local tissue impedance and ventilation per minute in addition to or instead of the above-described techniques based on cardiac electrical activity. It should be programmed to sense the presence of myocardial ischemia with a reasonable probability. In order to add specificity to the detection scheme, for example, the instrument is a threshold in which damage current is sensed and the patient's heart rate and / or effort level (measured by activity level or minute ventilation) is specified. It may be programmed to detect myocardial ischemia only if it is higher than the value.

Illustrative Embodiment To perform vasoactive therapy, a cardiac instrument is implanted in a patient's body with stimulation electrodes positioned near one or more coronary arteries. An example of a bipolar stimulation electrode 400 incorporated into a lead 410 inserted into a coronary sinus or cardiac vein 420 to be positioned proximate to a branch of the coronary artery 430 is shown. The lead 410 may have mechanical means to facilitate positioning of the stimulation electrode in the vein adjacent to the coronary artery to be stimulated. FIG. 5A shows an embodiment in which the lead has a stent 520 and the electrode 500 is provided on the strut 510 so that the strut expands and strikes the vein wall, thus pressing the electrode against the adjacent arterial wall. FIG. 5B shows another embodiment having a steerable tip 460 that can be steered in such a way that lead 410 presses electrode 400 against the adjacent arterial wall. A stimulation lead may also be placed in the myocardium of an area determined to have microvascular dysfunction. Some patients with angina symptoms do not have occlusive lesions in their primary arteries. However, problems arise with these patients about their microvascular circulation. Vascular modulation therapy can be applied to these patients by targeting the myocardial capillary bed of these patients.

  After implantation and proper placement of the vasoactive stimulation electrode, the instrument may then be programmed with appropriate stimulation parameters to deliver vasoconstriction and / or vasodilation stimulation. Such stimulation parameters include pulse frequency, stimulation polarity (anode or cathode), pulse amplitude, pulse width, stimulation vector, and stimulation burst duration. In order to select the appropriate parameters, various stimulation parameters may be attempted while monitoring the patient's coronary blood flow, for example by coronary angiography, ultrasound flow sensing, perfusion scanning, magnetic resonance imaging or electrocardiography. good. The instrument may then be programmed with stimulation parameters suitable for vasodilation and / or vasoconstriction modes. The instrument is further vasodilated and / or according to one or more variables sensed by the instrument to increase or decrease the amount of vasoactive therapy delivered as appropriate and associated with myocardial ischemia. It may be programmed to automatically adjust the stimulation parameters according to the vasoconstriction mode. A look-up table may be constructed for this purpose, and this look-up table can be used to monitor a variety of sensed variables by monitoring sensed variables and coronary blood flow as the stimulation parameters are changing. Map values to various values of stimulation parameters. In this case, the instrument may be configured to automatically adjust the stimulation parameters in a closed loop manner in either vasodilation or vasoconstriction mode according to the sensed variable.

  Exemplary implantable cardiac devices for applying vasoactive therapy include one or more leads having stimulation electrodes that can be placed endocardially or myocardially proximate to the coronary artery. In this case, the stimulation electrodes so arranged are configured in one or more vasoactive stimulation channels. To localize the stimulation, the stimulation channel is preferably configured to deliver bipolar stimulation to the target arterial site. In an exemplary electrode arrangement for a vasoactive stimulation channel, a pair of bipolar stimulation electrodes are placed in a cardiac vein in communication with the coronary sinus to stimulate the coronary sinus or the branch of the left coronary artery. The instrument may then deliver a stimulation pulse through the vasoactive stimulation channel, where the stimulation parameters are selected to produce either vasodilation or vasoconstriction. In order to prevent myocardial capture, a vasoactive stimulation pulse may be delivered in synchrony with the detected cardiac electrical activity during the period in which the heart is refractory. For this purpose, the same or different electrodes used for vasoactive stimulation may be incorporated into a monopolar or bipolar ventricular sensing channel. The vasoactive stimulation pulse may then be delivered as a burst of pulses for a specified period following detection of a ventricular sense (ie, R wave). If the instrument also delivers ventricular pacing therapy, a burst of vasoactive stimulation pulses may also be delivered during a specified period after the ventricular pacing pulse.

  Although the instrument can be configured to deliver vasodilation or vasoconstriction stimulation pulses continuously, in most cases it is preferred to configure the instrument to deliver such stimulation intermittently. Thus, the instrument may be configured to operate in either a normal mode where no vasoactive therapy is applied, or a vasodilation and / or vasoconstriction mode in which vasoactive stimulation pulses are delivered. The instrument may also deliver other types of therapy, such as bradycardia pacing or cardiac resynchronization pacing, when operating in normal mode and / or vasoactive mode. When in vasodilation or vasoconstriction mode, delivered during ventricular sense or refractory period after ventricular pace for all cardiac cycles or for a specified portion of the cardiac cycle (eg every third cardiac cycle) Also good. In order to duty cycle vasoconstriction and / or vasodilation modes, the instrument may be configured to use one or more inlet and / or outlet conditions in controlling entry into and exit from the mode. . Inlet or outlet conditions can include, for example, elapsed time (eg, a specified time of day or elapsed time from a particular event), a patient switch (eg, magnetically actuated or contact actuated interfaced to an instrument controller) The switch received by the telemetry method, or a measured variable within or outside a specified range. Examples of such variables to be measured include electrograms indicating myocardial ischemia, heart rate, activity level, ventilation per minute, cardiac output, blood pressure, blood oxygen, blood pH and myocardial contractility (eg, by arterial pressure sensor). Features derived from the maximum dP / dt measured). Multiple entrance and / or exit conditions may also be ORed or ANDed together to form a composite exit or entrance condition. FIG. 6 illustrates an exemplary algorithm that executes the instrument controller to switch from normal mode to one of vasoconstriction and vasodilation modes. In step 601, the instrument determines whether an entry condition for switching to a particular vasoactive mode is met. If so, the instrument checks in step 602 if the exit conditions for that vasoactive mode are met. If so, the instrument returns to step 601. If not, in step 603, a mode switch to vasoactive mode is performed and step 604 proceeds to monitor for exit conditions. If the exit condition is met, the instrument returns to normal mode at step 605 and returns to step 601 to monitor for the entrance condition.

  In an exemplary embodiment, the instrument comprises one or more sensors that sense a variable that can be correlated to the occurrence of myocardial ischemia and senses the presence or absence of myocardial ischemia according to the sensed variable. Programmed to do. Sensors record electrograms, cardiac sensing channels that measure heart rate, accelerometers that measure activity levels or local heart motion, impedance sensors that are sensitive to local changes in tissue impedance that occur during ischemia, and / or It should be a minute ventilation sensor. In this case, the instrument operates in normal mode when no vasoactive therapy is being applied, and switches to vasodilation mode and / or vasoconstriction mode in response to sensed conditions and / or patient initiation commands. Composed. For example, the instrument can intermittently switch to vasoconstriction mode only if it follows a prescribed schedule but the sensed variable indicates that myocardial ischemia is not present. For example, the instrument can sense the patient's activity level (eg, reflecting heart rate, activity level and / or ventilation per minute) and the sensed variable is within a specified range It may be configured to switch intermittently to the vasoconstriction mode only. In this case, the controller switches to vasodilator mode whenever the sensed variable indicates that myocardial ischemia is present, and the sensed variable indicates that myocardial ischemia is not present. In some cases, it is programmed to operate intermittently in either vasoconstriction mode or normal mode at any time. The instrument may also be configured to switch from the normal mode to the vasodilation mode when it is determined by the sensed variable that myocardial ischemia is present. FIG. 7 shows an exemplary algorithm executed by the controller to switch between the normal mode and the vasoconstriction and vasodilation modes. In step 701, the instrument operates in a normal mode, which entails delivering some pacing therapy (eg, bradycardia or resynchronized pacing) or no pacing at all. There is a case. In step 702, the instrument checks whether ischemia is present. If myocardial ischemia is detected, the instrument operates in vasodilation mode at step 703 as long as ischemia is present. If no myocardial ischemia is present, in step 704, the instrument checks if it is time to switch to vasoconstriction mode. If so, the instrument determines in step 705 whether the measured effort level is below a specified value indicating that the patient is at rest. If the patient is at rest, the instrument operates in a vasoconstriction mode in step 706 and remains in that mode until the specified duration determined in step 707 has elapsed. In another embodiment, the patient comprises means for switching the instrument to a vasoconstriction mode, to a vasodilation mode when presented with symptoms of myocardial ischemia, and / or to a normal mode. Such means may be, for example, a patient operated switch interfaced to an instrument controller, such as a magnetically operated or contact operated switch. The patient may further comprise means for communicating to the instrument by telemetry, for example from a remote monitor, in order to issue a command to switch to the selected mode.

  In another embodiment, the myocardial region (fragile region) that is prone to ischemia is anatomically located. The ischemic area can be located by a number of means, such as ultrasound imaging, PET scanning, thallium scanning, and MRI perfusion scanning. A stimulation lead (e.g., a screw lead) is then skillfully placed to stimulate the myocardial capillary bed that delivers the stimulation to the located fragile region. In this case, the instrument may be programmed to deliver a vasodilator stimulus to the capillary bed when myocardial ischemia is sensed. Vasoactive therapies as described herein can also be combined with pacing therapies that alter the area wall stress to obtain a therapeutic effect. For example, pre-excited myocardial regions near the paced site during systole while myocardial regions located far from the paced site show increased wall stress and metabolic demand, Show reduced wall stress and metabolic demand. Such pre-excitation pacing may be used to intentionally stress specific myocardial regions for conditioning purposes and can be combined with vasoconstriction stimulation. Pre-excitation pacing can also be used to mechanically remove a load from a vulnerable myocardial region, for example when myocardial ischemia is sensed, and can be combined with vasodilator stimulation.

  The invention has been described in connection with the specific embodiments described above. It should be understood that these embodiments can be combined with each other in any manner deemed advantageous. Many substitutions, modifications and alterations will also be apparent to those skilled in the art. Such other substitutions, modifications, and alterations are within the scope of the present invention as set forth in the appended claims.

Claims (13)

A heart instrument,
An implantable housing that houses the electrical circuit;
A vasoactive stimulation electrode adapted to be placed proximate to the coronary artery;
A pulse generator connectable to the vasoactive stimulation electrode and outputting a vasoactive stimulation pulse;
A sensing channel for sensing cardiac electrical activity;
An impedance sensor for measuring cardiac blood flow;
A programmed controller to operate in vasodilation mode Normal mode or vasoactive stimulation pulses vasoactive stimulation pulses are not delivered is fed in such a way as to cause vasodilation of the coronary arteries, was closed,
The controller is programmed to deliver the vasoactive stimulation pulse in the vasodilation mode, wherein the delivery of the vasoactive stimulation pulse occurs concurrently with mechanical ventricular dilatation determined from measured cardiac blood flow. Ru is time, heart for the instrument.   The controller measures a heart rate from the sensed cardiac electrical activity, and when the heart rate has reached a value indicating that a particular patient has myocardial ischemia, The instrument of claim 1, wherein the instrument is programmed to switch to an extended mode. A switch operated by the patient;
The instrument of claim 1 or 2, wherein the controller is programmed to switch from the normal mode to the vasodilator mode upon actuation of the patient operated switch. A telemetry transceiver;
The controller is programmed to switch from the normal mode to the vasodilation mode upon receiving a telemetry command for switching from the normal mode to the vasodilation mode. The instrument according to Kaichi. A sensor for sensing a variable that can be correlated to the occurrence of myocardial ischemia in the patient;
4. The controller according to any one of claims 1 to 3, wherein the controller is programmed to switch from the normal mode to the vasodilator mode when the sensed variable indicates the occurrence of myocardial ischemia. Instruments.   6. The sensed variable that can be correlated to the presence of myocardial ischemia is selected from the group comprising features derived from sensed cardiac electrical activity, minute ventilation, and activity level. The instrument described.   The controller is programmed to switch from the vasodilation mode to the normal mode upon occurrence of a specified diastole exit condition, the exit condition not detecting the presence of myocardial ischemia, elapsed time, patient-operated switch 7. An instrument according to any one of the preceding claims, selected from the group comprising actuation and receipt of a telemetry command to end the mode.   The controller is further programmed to operate in a vasoconstriction mode in which vasoactive stimulation pulses are delivered during a cardiac refractory period determined from the sensed cardiac electrical activity in a manner that causes vasoconstriction of the coronary arteries. The instrument of any one of claims 1-6.   9. The instrument of claim 8, wherein the controller is programmed to intermittently switch from the normal mode or the vasodilation mode to the vasoconstriction mode according to a defined schedule.   9. The instrument of claim 8, wherein the controller is programmed to exit the vasoconstriction mode if other variables reflecting measured heart rate or effort level are greater than a specified threshold.   11. The instrument of any one of claims 1-10, wherein the controller is programmed to deliver a vasoactive stimulation pulse during a cardiac refractory period determined from the sensed cardiac electrical activity. The strut further comprising a lead having a stent provided with one or more vasoactive stimulation electrodes, wherein the struts expand to strike the vein wall and thus press the electrode against the adjacent arterial wall. The instrument as described in any one of 1-11 . 13. The instrument of claim 12 , wherein the lead has a steerable tip that is steerable to press the vasoactive stimulation electrode against the adjacent arterial wall.

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